The four valves of the human heart consist of either two or three pliable leaflets attached circumferentially to a fibrous skeletal annulus. Normally, heart valves function to open in one portion of the cardiac cycle, either systole or diastole, (depending on the valve), causing minimal resistance to forward blood flow, but close by hinging from the annulus during the other part of the cardiac cycle, with the leaflets (either two or three) coming into central contact with each other, such that retrograde flow is inhibited.
Heart valve regurgitation, or leakage occurs when the leaflets of the valve fail to come fully into contact. This can be congenital, or the result of a disease process. Regardless of the cause, the leakage interferes with heart function, since it allows the unintended flow of blood back through the valve. Depending on the degree of leakage, the backward flow can become a self-destructive influence on not only function, but also cardiac geometry. Alternatively, abnormal cardiac geometry can cause the leakage, and the two processes are “cooperative” in causing acceleration of abnormal cardiac function.
The result of a valve having significant regurgitation is that a pathological state develops in which blood may be simultaneously pumped both forward through the outflow valve of a chamber and backward through the inflow valve, decreasing forward cardiac output. Depending on the severity of the leakage, the capability and efficiency of the heart to pump adequate blood flow can be compromised. In the case of the two trio-ventricular valves, (the mitral and tricuspid), the process can be caused by myocardial infarction damaging papillary muscles located in the left (or right) ventricle, torn or abnormally elongated chordae tendineae, or in any valve through damaged valve structures by infection, degenerative processes, or stretching of the annulus such that leaflets no longer come into contact by virtue of the increased cross-sectional area. Stretching of the ventricle and increased distance between the papillary muscles can also cause leakage of the atrio-ventricular (A/V) valves.
At present, for the most part, regurgitant valves can be either surgically repaired or replaced, both currently requiring open-heart surgery, use of cardio-pulmonary bypass and stoppage of the heart. Because of the magnitude of the procedure, risk of death, stroke, and bleeding, respiratory, renal, and other complications is significant enough that many patients are not candidates for treatment. The heart or aorta must be cut open, and even when performed by very experienced surgeons, repairs can fail early, or, if initially successful, are not always durable over time.
In the case of the mitral valve, replacement with a prosthetic or bio-prosthetic valve is associated with a higher operative mortality than repair of the native valve, but does not result in recurrent regurgitation experienced after a repair. The higher mortality is thought to be the result of loss of the function of the papillary muscles of the left ventricle, which are attached to the mitral valve leaflets by cords known as chordae tendineae, which contribute to tethering of the leaflets and systolic shortening of the left ventricle. However, with preservation of these sub-valvular structures, the outcomes equalize, or may be better in severe cases with replacement and sub-valvular structure preservation. (See Ann Thorac Surg 2 81: 1153-61.)
Even though the prognosis of surgically untreated mitral regurgitation is poor, (see N Engl J Med 2 352:875-83), only 33% of patients with significant regurgitation are referred, due to age, co-morbidities, or physician preference (see European Journal of Cardio-thoracic Surgery 34 (2) 935-936).
In the face of a severe, life threatening pathological process with no treatment offered to a majority of patients due to the magnitude of the risks of currently available therapy, a simpler, less invasive approach to treatment, such as a percutaneous device that can effectively eliminate regurgitation, yet preserve annulo-ventricular in atrio-ventricular connectivity and function, is severely needed.
For this reason, there is widespread development currently underway for placement of valves into the aortic (see Circulation December 2002 p. 3006-3008), and Pulmonary, (see J. Am. Coll. Card., vol. 39, May 15, 2002, p. 1664-1669), positions. There are currently a variety of technologies for aortic replacement, but all generally have an expandable support structure for attached pliable leaflets, delivered either through the apex of the ventricle or retrograde through the aorta from the femoral artery (The Journal of Thoracic and Cardiovascular Surgery; October 2008, p 817-819).
Because of the asymmetry of the annuli, as well as the lack of rigidity, the same principals cannot be applied to the mitral and tricuspid valves, or in the aortic valve in the absence of calcification, as in most cases of aortic insufficiency. In the mitral position, several approaches have been pursued. Additionally, in the case of the mitral valve, radial expansion of a prosthetic replacement could impinge on the aortic valve, with which it shares a portion of its annulus along the anterior mitral leaflet.
Primarily, remodeling or alteration (to support or decrease the size) of the mitral annulus by various means has been a focus of intense interest. Some of the most tested of these are those that rely on the perceived anatomic proximity between the posterior annulus and the coronary sinus (see Webb, et al). Although initially promising, the coronary sinus has been shown in virtually all cases to course on the atrial side of the mitral annular plane, and averages 7 to 11 mm from the annulus, and the distances are variable. Moreover, the distances increase in subjects with mitral regurgitation. (See Choure, et al, J Am. Coll. Card.; Vol. 48, No. 10, 2.) The approach has been largely abandoned.
Another approach is the central apposition of the anterior and posterior leaflets at the midpoint, mimicking the so-called “Alfieri stitch”. The benefit comes from creation of central coaptation. Devices to create this reconfiguration have been tested and commercialized, but do not control regurgitation to the degree achieved in replacement.
In general, current heart valve replacement procedures generally require invasive surgery. This, of course, is a long, difficult and complex process and requires that the patient endure significant, invasive surgery. While various alternatives have been proposed to minimize this trauma, there is still a need in the art to further reduce such potential injury.